An in vitro system was established for the quantitative chemical transformation of the mouse epithelial cells Mus musculus castaneous epithalial (MMCE). These cells can also be transformed by C3H/MuLV in conjuction with 12-0-tetradecanoyl-phorbol-13-acetate (TPA). Transformed cell clones obtained from soft agar generally were virus nonproducers. The purpose of these experiments was to sequence-label TPA-promotable cellular tumor genes and thus make possible their isolation by molecular cloning. MMCE cells have also appeared to provide the first system for two-stage carcinogenesis in culture with ethylnitrosourea (ENU) as carcinogen and TPA as promoting agent. Clones of transformed cells were examined for transformation-sensitive glycoproteins. MMCE cells were also transformed by a new transforming virus 3611-MSV and the pattern of glycoprotein changes that were induced was determined. These cells show a different profile of glycoprotein changes and two new transformation-induced cellular proteins were identified. The observation of cocarcinogenesis of MMCE cells with MuLV and TPA prompted a search for factors homologous to TPA in normal sera. Such a transforming factor was found and purified from normal mouse serum.